JP2021143151A - Oral composition - Google Patents

Abstract

To provide an oral composition that allows allantoin or a derivative thereof to be absorbed well into oral mucosa and has a good taste and a good feeling of use.SOLUTION: An oral composition contains (A) allantoin or a derivative thereof, (B) a polyoxyethylene hardened castor oil with an average number of moles of added ethylene oxide of 5-10 mol, of 0.1-3 mass%, and (C) vitamin E or a derivative thereof of 0.01-3 mass%.SELECTED DRAWING: None

Description

The present invention relates to an oral composition that promotes absorption of allantin or a derivative thereof into the oral mucosa such as gingiva, has excellent absorbability, has a good taste, and is suitable for preventing or suppressing periodontal diseases such as gingival inflammation. ..

As a water-soluble active ingredient to be blended in an oral composition, for example, allantin or a derivative thereof has an activity of activating cell functions and a tissue repairing action, and is useful for prevention or suppression of periodontal diseases such as gingival inflammation. It has been known. In order for this water-soluble active ingredient to act efficiently, absorption and penetration into the oral mucosa such as gingiva are important.
However, the oral cavity is different from the skin in that saliva is always supplied and wet, and the oral composition is often rinsed with water after being applied to the oral cavity, and the mucosal surface of the wet gingiva and its surface. It is in an environment where it is difficult to absorb and permeate water-soluble components into the interior. Therefore, it is difficult to sufficiently promote the absorption of the water-soluble active ingredient into the oral mucosa surface such as gingiva and the inside thereof, and the effect of promoting the absorption of the unstable and easily decomposed allantin or its derivative into the oral mucosa is improved. Was an issue.

It has been proposed in Patent Document 1 (Japanese Unexamined Patent Publication No. 2015-205826) that a specific fatty acid or ester is blended to improve the absorption of the water-soluble active ingredient blended in the oral composition into the oral tissue. However, there is a problem in usability, and it has been proposed that the addition of a specific fragrance component is effective for solving the lack of refreshing feeling (Patent Document 2; Japanese Patent Application Laid-Open No. 2016-222582).
As an active ingredient for preventing or suppressing periodontal disease such as gingival inflammation, a poorly water-soluble vitamin E or a derivative thereof having a peripheral circulation promoting action (blood circulation promoting action) of gingival tissue is also an oral composition such as a dentifrice composition. Nonionic surfactants contribute to these stable formulations, and polyoxyethylene (20) hardened gum oil and the like are widely used because of their good usability. In Patent Document 3 (Japanese Unexamined Patent Publication No. 2017-214297), an oil-soluble specific fatty acid or ester is blended in order to promote oral absorption of a water-soluble active ingredient, and polyoxyethylene is further blended with a poorly water-soluble tocopherol or a derivative thereof. By blending an alkali metal salt of an alkyl ether, an inorganic acid or an organic acid, tocopherol or a derivative thereof is blended at the same time while ensuring its storage stability, and the oily odor caused by a specific fatty acid or ester is suppressed to improve the usability. It is improving.
As described above, the specific fatty acid or ester may cause a problem in usability depending on the composition, and it has been desired to develop a new technique for promoting the absorption of the water-soluble active ingredient into the oral mucosa.

Japanese Unexamined Patent Publication No. 2015-205826 Japanese Unexamined Patent Publication No. 2016-222582 Japanese Unexamined Patent Publication No. 2017-214297 Japanese Unexamined Patent Publication No. 2009-149537 Japanese Unexamined Patent Publication No. 2018-43933

The present invention has been made in view of the above circumstances, and an object of the present invention is to provide an oral composition having excellent absorption of allantoin or a derivative thereof into the oral mucosa, having a good taste and a good usability.

As a result of diligent studies to achieve the above object, the present inventors have made a polyoxyethylene hydrogenated castor oil in which the average number of moles of ethylene oxide added is equal to or less than a specific value in an oral composition containing allantin or a derivative thereof. When Vitamin E or a derivative thereof is blended in combination, the absorption of the component (A) into the oral mucosa is promoted, the bitterness is suppressed and the taste is good, and after the component (A) is stored. It was found that it can be stably blended. That is, according to the present invention, (A) allantin or a derivative thereof, (B) polyoxyethylene hydrogenated castor oil having an average addition mole number of 5 to 10 moles of ethylene oxide, and (C) vitamin E or a derivative thereof are contained. It has been found that the composition for oral cavity is excellent in absorption of the component (A) into the oral mucosa, has a good taste and a good usability, and has good storage stability of the component (A). It came to make.

In the present invention, by blending the component (B) with the component (A) in combination, the absorption of the component (A) into the oral mucosa is promoted, and the component (A) can be effectively absorbed and permeated. This absorbency promoting action cannot be obtained when polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 20 mol is used instead of the component (B), and is specific to the component (B). It was an action. When the component (C) is further added, surprisingly, the bitterness caused by the combined use of the components (A) and (B) is suppressed and reduced by the component (C), whereby the good taste is maintained. The absorption of the component (A) into the oral mucosa could be enhanced.
Therefore, the oral composition of the present invention can secure a good feeling of use, promote the absorption of the component (A) into the oral mucosa, and allow the component (A) to be absorbed by the oral mucosa at a high rate. .. In addition, the storage stability of the component (A) can be ensured, and the composition can be stably blended even after storage at a high temperature (50 ° C.), and the pH of the composition is set to pH 6.4 or less, which is relatively stable for the component (A). You can also do it.
In Patent Documents 4 and 5 (Japanese Patent Laid-Open Nos. 2009-149537 and 2018-43933), ascorbic acid phosphate using polyoxyethylene hydrogenated castor oil having an average addition molar number of ethylene oxide of 5 to 10 is used. It is an improvement in the permeability of the salt to the oral mucosa, and is effective when the pH of the oral composition is 6.5 or more. On the other hand, the present invention is a technique relating to allantin or a derivative thereof, which is unstable and easily decomposed particularly in the basic region, and the improvement of the oral mucosal absorption of the component (A) by the components (B) and (C). And the bitterness is suppressed, and even if the pH of the oral composition is set to 6.4 or less, the above-mentioned action and effect are excellent, and rather, it is remarkable at the pH value or less.

Therefore, the present invention provides the following oral compositions.
(A) Allantoin or its derivatives,
An oral composition comprising (B) polyoxyethylene hydrogenated castor oil having an average addition mole number of 5 to 10 moles of ethylene oxide and (C) vitamin E or a derivative thereof.

According to the present invention, it is possible to provide an oral composition having excellent absorption of the component (A) into the oral mucosa, good taste, and storage stability of the component (A). The oral composition of the present invention can absorb and permeate the component (A) into the oral mucosa such as gingiva to efficiently express its medicinal effect, and is used for prevention or suppression of periodontal diseases such as gingiva. It is useful.

Hereinafter, the present invention will be described in more detail. The oral composition of the present invention contains (A) allantoin or a derivative thereof, (B) a specific polyoxyethylene hydrogenated castor oil, and (C) vitamin E or a derivative thereof.

(A) Allantoin or a derivative thereof has a repairing action on gum tissue and is an active ingredient for prevention or suppression of periodontal disease.
Examples of allantoin or a derivative thereof include allantoin, allantoin chlorohydroxyaluminum, allantoin dihydroxyaluminum and the like, and one or more of these can be used.

The blending amount of (A) allantoin or a derivative thereof is preferably 0.01 to 0.5% (mass%, the same applies hereinafter) of the entire composition, and more preferably 0.05 to 0.2%. When the blending amount is in the above range, the absorption of the component (A) into the oral mucosa is sufficiently promoted and excellent, and the bitterness is sufficiently suppressed. In addition, the storage stability of the component (A) can be sufficiently obtained.

The component (B) is a polyoxyethylene hydrogenated castor oil having an average number of moles of ethylene oxide added (hereinafter, sometimes abbreviated as EO) of 5 to 10 moles, and promotes absorption of the component (A) into the oral mucosa. Acts as an agent.
The EO of polyoxyethylene hydrogenated castor oil is 5-10 mol, preferably 5-7 mol. It is important that the EO is in the above range to promote the absorption of the component (A) into the oral mucosa, and when the EO exceeds 10 mol, the effect of promoting the absorption of the component (A) into the oral mucosa is inferior.

The blending amount of the component (B) is preferably 0.1 to 3%, more preferably 0.2 to 2% of the entire composition. When the blending amount is 0.1% or more, the absorption of the component (A) into the oral mucosa is promoted, and the absorbability is sufficiently excellent. When it is 3% or less, the absorbency is sufficiently excellent, the bitterness does not become too strong, and the bitterness can be sufficiently suppressed.

(C) Vitamin E or a derivative thereof acts as a bitterness suppressant in a combination system of the components (A) and (B).
Vitamin E or a derivative thereof is, for example, tocopherols such as d-α-tocopherol, dl-α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, and esters thereof, such as acetic acid, nicotinic acid, succinic acid, and linolenic acid. Esters with organic acids such as acids, particularly organic acids having 1 to 20 carbon atoms, and salts thereof can be used. Specific examples of the vitamin E derivative include tocopherol acetate such as d-α-tocopherol acetate and dl-α-tocopherol acetate, tocopherol nicotinate such as d-α-tocopherol nicotinate and dl-α-tocopherol nicotinate. , D-α-tocopherol succinate, tocopherol succinate such as dl-α-tocopherol succinate, tocopherol linolenate such as d-α-tocopherol linolenic acid, dl-α-tocopherol linolenate, tocopherol calcium succinate. .. These can be used alone or in combination of two or more.

The blending amount of (C) Vitamin E or a derivative thereof is preferably 0.01 to 3%, more preferably 0.05 to 2% of the total composition. When the blending amount is 0.01% or more, the bitterness is sufficiently suppressed and the taste is good. When it is 3% or less, the action of the component (B) is maintained, and the effect of promoting the absorption of the component (A) into the oral mucosa is sufficiently excellent.

Further, (A) / (B) indicating the quantitative ratio of the component (A) to the component (B) is preferably 0.005 to 5 as a mass ratio, and more preferably 0.05 to 1. When the mass ratio of (A) / (B) is 0.005 or more, the absorption of the component (A) into the oral mucosa is further promoted, and when the mass ratio is 5 or less, the bitterness is sufficient. It is suppressed.

The mass ratio of (A) / (C) indicating the quantitative ratio of the component (A) to the component (C) is preferably 0.01 to 10 and more preferably 0.05 to 2. When the mass ratio of (A) / (C) is within the above range, the absorption of the component (A) into the oral mucosa is sufficiently excellent, and the bitterness is further suppressed and reduced. If it is less than 0.01, the absorption of the component (A) into the oral mucosa may decrease, and if it exceeds 10, the bitterness may not be sufficiently suppressed.

Further, (B) / (C), which indicates the amount ratio of the component (B) to the component (C), is preferably 0.2 to 60 in mass ratio, more preferably 0., from the viewpoint of suppressing bitterness. It is 2 to 40, particularly preferably 0.4 to 20. When the mass ratio of (B) / (C) is 60 or less, the bitterness is sufficiently suppressed.

The oral composition of the present invention preferably has a pH (25 ° C.) of 4 to 6.4, more preferably 5 from the viewpoint of the present action effect, particularly suppression of bitterness and storage stability of the component (A). ~ 6. When the pH is 6.4 or less, the stability of the component (A) over time is sufficiently ensured, and when the pH is 4 or more, the bitterness is sufficiently suppressed.
A pH adjuster can also be added, and the pH adjuster includes, for example, citric acid such as citric acid and sodium citrate or a salt thereof, malic acid or a salt thereof, phosphoric acid or a salt thereof, sodium hydroxide and the like. Examples thereof include alkali metal hydroxides and bicarbonates.

The oral composition of the present invention can be prepared in the form of a paste, liquid or the like into a dentifrice composition such as dentifrice, liquid dentifrice, or dentifrice, a mouthwash composition, or a mouth spray. It can be made, and is particularly suitable as a dentifrice composition or a mouthwash composition, particularly as a dentifrice composition.

In addition to the above-mentioned components, the oral composition of the present invention includes known additive components (pharmacologically acceptable carriers) that can be used in the oral composition as long as the effects of the present invention are not impaired. The active ingredient can be blended. Examples of such additive components include abrasives, thickeners, binders, surfactants, sweeteners, preservatives, colorants, fragrances, solvents and the like. These components and water can be mixed and prepared. The blending amount shown below is the amount with respect to the entire composition.

Abrasives are silica-based abrasives such as silicic acid anhydride, silica gel, aluminosilicate, and zirconosilicate, anhydrous or dihydrate of calcium dibasic phosphate, calcium phosphate-based abrasives such as calcium tribasic phosphate, calcium pyrophosphate, and water. Examples thereof include aluminum oxide, aluminum oxide, calcium carbonate, and synthetic resin-based abrasives. The blending amount of the abrasive is preferably 2 to 50%, particularly 10 to 40%.

Examples of the viscous agent include sugar alcohols such as sorbitol, xylitol, erythritol and reduced starch saccharified product, and polyhydric alcohols such as glycerin, propylene glycol and polyethylene glycol. The blending amount of the thickener is usually 5 to 50%.

The binder is alginic acid such as sodium alginate and propylene glycol alginate or a derivative thereof, gums such as xanthan gum, cellulose derivatives such as sodium carboxymethyl cellulose and hydroxyethyl cellulose, and organic viscosity such as sodium polyacrylate, polyvinyl alcohol and polyvinylpyrrolidone. Examples thereof include binders and inorganic binders such as thickening silica. The blending amount of the binder is usually 0.1 to 10%.

As an arbitrary surfactant, an anionic surfactant, a nonionic surfactant other than the component (B), a cationic surfactant, and an amphoteric surfactant can be blended.
Examples of the anionic surfactant include alkyl sulfates such as sodium lauryl sulfate, acyl taurine salts such as sodium lauroylmethyl taurine, acyl sarcosates, and acyl amino acid salts. The blending amount of the anionic surfactant, particularly sodium lauryl sulfate, is preferably 0.001 to 10%, more preferably 0.01 to 5%, from the viewpoint of exhibiting the effect of the present invention.
The nonionic surfactant does not have to be blended in addition to the component (B) (blending amount 0%), but it can also be blended within a range that does not interfere with the effect of the present invention. In this case, the blending amount is preferable. Is 0.5% or less, more preferably 0.2% or less. Optional nonionic surfactants include, for example, sugar fatty acid ester, sugar alcohol fatty acid ester, sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene higher alcohol ether.
Examples of the cationic surfactant include quaternary ammonium salts such as alkylammonium type and alkylbenzylammonium salt, and examples of amphoteric surfactant are betaine type such as alkylbetaine and fatty acid amide propyl betaine, 2-alkyl-N. Examples thereof include alkylimidazole types such as −carboxymethyl-N-hydroxyethyl imidazolium betaine.
The blending amount of any surfactant is 0.01-10%, especially 0.1-5%.

Examples of the sweetener include sodium saccharin, aspartame, stebioside, stevia extract, paramethoxycinnamic aldehyde and the like.
Examples of the preservative include paraoxybenzoic acid esters such as methylparaben, ethylparaben and butylparaben, benzoic acid or salts thereof.
Examples of the colorant include Blue No. 1, Yellow No. 4, Titanium Dioxide and the like.

Fragrances are peppermint oil, sparemint oil, anis oil, eucalyptus oil, winter green oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamon oil, coriander oil, mandarin oil, lime. Oil, lavender oil, rosemary oil, laurel oil, camomill oil, caraway oil, majorum oil, bay oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, grapefruit oil, sweetie oil , Yuzu oil, iris concrete, absolute peppermint, absolute rose, orange flower and other natural fragrances, and processing of these natural fragrances (pre-reservoir cut, rear-reservoir cut, distilling, liquid extraction, essence, powder fragrance Perfume, menthol, carboxylic, anator, cineole, methyl salicylate, synamic aldehyde, eugenol, 3-l-mentoxypropane-1,2-diol, timole, linalol, linaryl acetate, limonene, menton , Menthylacetate, N-substituted-paramentan-3-carboxamide, pinen, octylaldehyde, citral, pregon, calvier acetate, anisaldehyde, ethylacetate, ethylbutyrate, allylcyclohexanepropionate, methylanthranilate, ethylmethyl Single flavors such as phenylglycidate, vanillin, undecalactone, hexanal, butanol, isoamyl alcohol, hexenol, dimethylsulfide, cycloten, furfural, trimethylpyrazine, ethyllactate, ethylthioacetate, strawberry flavor, apple flavor, banana flavor , Pineapple flavor, grape flavor, mango flavor, butter flavor, milk flavor, fruit mix flavor, tropical fruit flavor, and other blended flavors that can be used in combination with known flavoring materials used in oral compositions. It is not limited to the fragrances described in the examples.
The blending amount of the fragrance is not particularly limited, but it is preferable to use 0.000001 to 1% of the above fragrance material in the composition, and the fragrance for fragrance using the above fragrance material is 0. It is preferable to use 1 to 2%.

The active ingredient is an ingredient other than the ingredient (A) and further, such as a nonionic bactericide, a cationic bactericide, an enzyme such as dextranase, and fluorine such as sodium fluoride and sodium monofluorophosphate. Examples include compound-containing compounds, water-soluble phosphate compounds, sodium chloride, potassium nitrate, aluminum lactate, plant extracts, anti-dental agents, and anti-plaque agents. The blending amount of the active ingredient is an effective amount within a range that does not interfere with the effect of the present invention.

Hereinafter, the present invention will be specifically described with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. In the following examples,% indicates mass% unless otherwise specified.

[Examples, comparative examples]
Oral compositions (toothpaste) having the compositions shown in Tables 1 to 5 were prepared by a conventional method and evaluated by the following method. The results are also shown in the table. In the table, the values in parentheses of polyoxyethylene hydrogenated castor oil are the average number of moles of ethylene oxide added.

(1) Method for evaluating the absorbability of allantoin or a derivative thereof A human three-dimensional epidermis model (LabCite EPI-MODEL 24, manufactured by J-TEC Co., Ltd.) was cultured overnight in the attached medium. Transfer the cup in which the epidermis model was cultured to a 24-well plate containing PBS (phosphate buffered saline), and inject 50 μL each of the oral composition diluted 3-fold with artificial saliva into the surface of the epidermis model. Allowed to stand for minutes. 50 μL of water was added to the surface of the epidermis model after standing, and washing by pipetting was repeated twice. The washing liquid was discarded, 50 μL of water was added to the surface of _{the epidermis model, and after culturing for 6 hours (37 ° C., 5% CO 2} ), the epidermis model was taken out and removed. Allantoin or its derivative permeated through PBS was quantified by HPLC under the following test conditions by the absolute calibration curve method, and the amount absorbed into the epidermis model was determined.
(Used equipment)
・ Pump: Shimadzu LC-20AD
・ Sample introduction section: Shimadzu Corporation SIL-20AC
・ Detector: Shimadzu Corporation SPD-20A
・ Column constant temperature bath: Shimadzu Corporation CTO-20AC
・ Eluent flow rate: 1 mL / min
(Test conditions)
-Detector: Ultraviolet absorptiometer (measurement wavelength: 210 nm)
-Column: Inertsil NH ₂ (diameter 4.6 mm x length 250 mm, particle size 5 μm)
-Column temperature: 35 ° C
-Eluent: Acetonitrile / phosphate buffer solution mixture (4: 1)
The absorption rate (%) when the absorption amount of allantoin or its derivative of the oral composition of Comparative Example 1 was set to 100% was calculated, and from the obtained absorption rate, the absorption of allantoin or its derivative was performed according to the following evaluation criteria. The sex (absorption of the component (A)) was determined, and the absorbability to the oral mucosa was evaluated.
Evaluation criteria ◎: Over 150% ○: Over 100% 150% or less ×: 100% or less

(2) Evaluation method of usability (no bitterness) Nine subject monitors extruded 1 g of the oral composition filled in a general laminated tube container from the container, placed it on a toothbrush, and placed the oral cavity in a normal manner. The taste (bitter taste) when the inside was washed was judged by the following scoring criteria.
Rating criteria 4 points: No bitterness 3 points: Almost no bitterness 2 points: Bitterness but acceptable 1 point: Unacceptable bitterness The feeling of use (no bitterness) was evaluated according to the evaluation criteria of.
Evaluation criteria:
⊚: 3.5 points or more ○: 3.0 points or more and less than 3.5 points ●: 2.0 points or more and less than 3.0 points ×: less than 2.0 points

(3) Method for evaluating storage stability of allantoin or its derivative over time The oral composition filled in a general laminated tube container was stored in a constant temperature bath at 50 ° C. or −5 ° C. for 2 weeks. After allowing these to stand at room temperature, 1.5 g of the oral composition is extruded from the container, separated, added 20 mL of 80% ethanol, shaken for 15 minutes, and centrifuged (3,000 rpm, 10 minutes). , Allantoin or its derivative in the supernatant was quantified by the absolute calibration curve method by HPLC under the following test conditions, and the content of allantoin or its derivative in the product stored at 50 ° C. and the product stored at −5 ° C. was calculated.
(Used equipment)
・ Pump: Shimadzu LC-20AD
・ Sample introduction section: Shimadzu Corporation SIL-20AC
・ Detector: Shimadzu Corporation SPD-20A
・ Column constant temperature bath: Shimadzu Corporation CTO-20AC
・ Eluent flow rate: 1 mL / min
(Test conditions)
-Detector: Ultraviolet absorptiometer (measurement wavelength: 273 nm)
-Column: Inertsil NH ₂ (diameter 4.6 mm x length 250 mm, particle size 5 μm)
-Column temperature: 35 ° C
-Eluent: Acetonitrile / phosphate buffer solution mixture (4: 1)
Calculate the residual rate (%) of allantoin or its derivative from the ratio of the content of allantoin or its derivative stored at -5 ° C when the content of allantoin or its derivative is 100%, and use the following evaluation criteria. The storage stability of allantoin or its derivative over time (storage stability of component (A)) was evaluated.
Evaluation Criteria ⊚: Residual rate of allantoin or its derivative is 95% or more ○: Residual rate of allantoin or its derivative is 90% or more and less than 95% ×: Residual rate of allantoin or its derivative is less than 90%

＊；（Ｂ）成分を含まない比較例１は、苦味が発現しなかった。

*; In Comparative Example 1 containing no component (B), no bitterness was expressed.

Claims (6)

(A) Allantoin or its derivatives,
An oral composition comprising (B) polyoxyethylene hydrogenated castor oil having an average addition mole number of 5 to 10 moles of ethylene oxide and (C) vitamin E or a derivative thereof. The oral composition according to claim 1, wherein the pH of the composition at 25 ° C. is 4 to 6.4. The oral composition according to claim 1 or 2, wherein (A) / (B) has a mass ratio of 0.005 to 5, and (A) / (C) has a mass ratio of 0.01 to 10. The oral composition according to any one of claims 1 to 3, wherein (B) / (C) has a mass ratio of 0.2 to 60. The content of the component (A) is 0.01 to 0.5% by mass, the content of the component (B) is 0.1 to 3% by mass, and the content of the component (C) is 0.01 to 3% by mass. The oral composition according to any one of claims 1 to 4. The oral composition according to any one of claims 1 to 5, which is a dentifrice composition.